The present invention relates generally to treatment methods using donor blood and preparations made from donor blood. More particularly, the invention describes subjecting a donor to a remote conditioning procedure prior to collecting or processing blood therefrom. As a result of such procedure, blood and blood-derived products obtained from the donor may contain certain biologically active substances. When administered to a treatment subject, these substances may provide a clinically desired health effect or trigger further release of substances causing a health benefit such as for example systemic protection against ischemia-reperfusion injury or reducing systemic inflammation.
In the broadest context, the term “conditioning” is defined as the use of stress to yield an improved health outcome. The best known example of conditioning is physical exercise, which of course yields multiple health benefits. Another example is fasting or alternate-day fasting, which also induces many health benefits including a number of reduced disease susceptibilities. For the purposes of this description, the term “conditioning” is defined in a narrower medical context to mean the application of a controlled biological stress to obtain a specific health benefit, mitigate against an anticipated negative health effect including an effect from an anticipated extended biological stress applied at a later time. Furthermore, the term “remote conditioning” is used herein to describe a plurality of repeated intermittent applications of a sub-lethal controlled biological stress to a suitable tissue bed or the whole body of a subject. Importantly, these repeated intermittent applications of controlled biological stress are conducted over predefined periods of time and alternated with predefined periods of time when the biological stress is withdrawn—so as to allow for a biological recovery to take place inbetween applications of the biological stress. The notion of “remote” in the term “remote conditioning” is used to define the circumstances where the health benefit is defined in a tissue bed or an organ other than the tissue bed, which is used to apply the biological stress, which may also include the whole body.
Transfusions of whole blood and blood components and products derived from whole blood are broadly known to provide a great deal of health benefit to subjects in need thereof. Examples of such treatments include blood transfusions to subjects experiencing moderate to severe blood loss. Transfusions of platelets, plasma, or red blood cells are widely used to elevate depressed blood pressure, improve organ perfusion and restore homeostasis in subjects with reduced blood volume or reduced cell count. Yet such transfusions are known to also cause a massive systemic inflammatory response throughout the body of the recipient. Intra-operative blood transfusions for example are known to cause a release of inflammatory mediators in various vascular beds. There is a need for treatment methods and blood-derived products that are designed to minimize such negative effects of traditional blood transfusions.
Remote conditioning is generally known to provide a variety of health benefits to the same subject that it is applied to. One known example is remote ischemic conditioning in which a series of intermittent occlusions of blood flow to a suitable tissue bed (for example a leg or an arm of the subject) is known to provide protection against subsequent ischemia-reperfusion injury. For patients with a heart attack for example, such therapy has been shown to significantly reduce the size of the final myocardial infarction.
Direct application of remote conditioning to a treatment subject has a number of limitations. In emergency circumstances—for example for a subject with severe blood loss as a result of an accident or trauma—there is a need for an immediate initiation of blood transfusion to restore organ perfusion and relieve hypotension. There is no time available to conduct a traditional remote conditioning procedure, which lasts typically 40 min or so. After the blood transfusion is initiated, the inflammatory reaction may soon be triggered and so applying a traditional remote conditioning procedure may not provide the desired effect or may not achieve its full therapeutic potential. Other circumstances when direct application of remote conditioning to the treatment subject is difficult may be the situations of severe trauma in which access to a tissue bed suitable for applying remote conditioning may not be available.
Accordingly, there is a need to overcome the limitations of the prior art and to provide treatment methods and blood-derived products designed to minimize inflammation or other negative health consequences upon their immediate use, while providing immediate and full health benefits to the treatment subject.